Twenty years of combinatorial antibody libraries, but how well do they mimic the immunoglobulin repertoire?
Twenty years of combinatorial antibody libraries, but how well do they mimic the immunoglobulin repertoire?
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组合抗体库已有二十年历史，但它们对免疫球蛋白库的模拟效果如何？
DOI：
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发表时间：
2009
影响因子：
11.1
通讯作者：
M. Persson
中科院分区：
文献类型：
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作者：
M. Persson
组合抗体库今年庆祝其成立20周年。1989年，第一个功能性抗体从免疫小鼠的组合抗体库中分离出来（1）。很明显，该技术还将有助于产生纯人类单克隆抗体用于医疗用途，这是不可能实现的基于细胞的方法分离单克隆抗体使用的时间。在这些抗体文库中，来自B淋巴细胞的mRNA（编码数百万或甚至数十亿的抗体重链和轻链）通过PCR技术被拯救，并最常在噬菌体上表达为功能性抗体，这允许分离具有特定特征的克隆，例如，与靶分子、细胞类型或组织结合（2，3）。文库可以从免疫个体产生，偏向于针对免疫原的克隆，或者尽可能多样化，产生所谓的天然文库，理论上可以从其中分离针对任何抗原的抗体。该技术是如此强大，以至于最常搜索的抗体类型的分离是成功的。也许是因为实际结果很容易实现，但更重要的是因为文库太大，无法用现有的核苷酸测序方法进行充分分析，直到现在才能评估这些文库模拟免疫系统的效果。在本期PNAS中，Glanville等人（4）首次深入表征了一个非常大的人类IgM抗体幼稚库，该库来自>650个个体供体，包含>3 × 10 ...
Combinatorial antibody libraries celebrate their 20th anniversary this year. In 1989, the first functional antibodies were isolated from a combinatorial antibody library derived from an immunized mouse (1). It was immediately evident that the technology would also lend itself to the generation of purely human monoclonal antibodies for medical use, which was not possible to achieve with the cell-based approaches for isolation of monoclonal antibodies used at the time. In these antibody libraries, mRNAs from B lymphocytes, coding for millions or even billions of the antibody heavy and light chains, are rescued by PCR technology and expressed as functional antibodies most often on phage that allow isolation of clones with particular characteristics, e.g., binding to a target molecule, cell type, or tissue (2, 3). The libraries can be created from immune individuals, biased for clones against the immunogen, or be as diverse as possible, producing so-called naive libraries from which theoretically antibodies to any antigen may be isolated. The technology is so robust that isolation of the type of antibodies searched for most often is successful. Maybe because practical results are easy to achieve, but more importantly because the libraries have been too large to adequately analyze with available nucleotide sequencing methods, just how well these libraries mimic the immune system has not been possible to assess until now. In this issue of PNAS, Glanville et al. (4) provide the first in-depth characterization of a very large naive library of human IgM antibodies, derived from >650 individual donors and comprising >3 × 10 …
影响因子：
56.9
作者：
SMITH, GP
通讯作者：
SMITH, GP